The heiGHt Trial evaluated 161 treatment-naïve children with GHD randomized in a 2:1 ratio to receive either once-weekly TransCon hGH (0.24 mg/kg/week subcutaneously, n=105) or daily Genotropin (34 µg/kg/day or 0.24 mg/kg/week subcutaneously, n=56) for 52 weeks. The trial met its primary objective, demonstrating that TransCon hGH was observed to be non-inferior and, as a bonus, superior to daily hGH on the primary endpoint of annualized height velocity (AHV) at 52 weeks.

In the primary analysis of the intent-to-treat population using ANCOVA, TransCon hGH demonstrated an AHV of 11.2 cm/year compared to 10.3 cm/year for the daily hGH. The treatment difference was 0.86 cm/year, with a 95-percent confidence interval of 0.22 to 1.50 cm/year. The AHV for TransCon hGH was significantly greater than the daily hGH (p=0.0088).

The AHV was greater for TransCon hGH than for the daily hGH at each visit, with the treatment difference reaching statistical significance from and including week 26, onward. The incidence of poor responders (AHV < 8.0 cm/year) was 4 percent and 11 percent in the TransCon hGH and daily hGH arms, respectively. All sensitivity analyses completed from the trial support the primary outcome, indicating the robustness of these results.

“The heiGHt Trial results ... represent a potential breakthrough for patients and future treatment options for growth hormone deficiency,” said Jan Mikkelsen, Ascendis Pharma’s president and CEO. “We believe these results provide a validation of our TransCon technology platform, which forms the basis of our endocrinology pipeline and has potential application in other therapeutic areas.”

Results from the trial indicate that TransCon hGH was generally safe and well tolerated, with adverse events consistent with the type and frequency observed with daily hGH therapy and comparable between arms of the trial. No serious adverse events related to study drug were observed in either arm. No treatment-emergent adverse events leading to discontinuation of study drug were observed in either arm.

“We are thankful to all those who participated in this important global trial,” noted Dr. Jonathan Leff, Ascendis’ chief medical officer. “Our goal is to alleviate the burden of daily injections so every child has a better opportunity to achieve normal adult height and overall endocrine health—and to look forward to a healthy future.”

These heiGHt Trial data were presented for the first time as an oral presentation on Sunday, March 24, at ENDO 2019 by investigator Dr. Paul Thornton, a pediatric endocrinologist at Cook Children’s Medical Center in Fort Worth, Texas.

“This is exciting news for all of those living with GHD, including our families at Cook Children’s, because we have shown that a single once-weekly dose of TransCon hGH was just as safe and works as well or better than daily growth hormone,” noted Thornton. “Now, the heiGHt Trial has shown that children with GHD can grow effectively on one shot a week.”

The TransCon hGH Phase 3 program includes the heiGHt, fliGHt and enliGHten Trials. Top-line data for the fliGHt Trial, evaluating TransCon hGH in subjects who switch from daily hGH, are expected in the second quarter of 2019. enliGHten is a long-term extension that provides subjects from the heiGHt and fliGHt Trials with the opportunity to continue once-weekly TransCon hGH treatment.

Ascendis plans a clinical database lock for the TransCon hGH Phase 3 program in the third quarter of 2019. Subsequently, the company intends to submit a Biologics License Application with the U.S. Food and Drug Administration for TransCon hGH to treat pediatric GHD in the first half of 2020.

According to Canaccord Genuity biotechnology analyst Michelle Gilson in an investor note related to the trial news: “We previewed the data ... and outlined our expectation for non-inferiority; however, the superiority result is above our expectation and we view as likely to create a competitive moat for programs behind TransCon GH in the clinic. Notably, the superiority result could create a positive dialogue with payers, especially as TransCon GH should be the only long-acting GH option at time of launch.”

“Recombinant (daily) growth hormone market in U.S. is ~$3.5 billion, and we anticipate it could grow to >$4 billion with a weekly option based on increased compliance and persistence,” Gilson continued. “We estimate ~16,000 treatable pediatric GHD patients in the U.S., and anticipate TransCon GH could move quickly to address next indications where rGH is approved. We anticipate Ascendis will launch TransCon GH beginning in 1H20 in the U.S. and E.U. shortly following. These superiority results may help uptake in E.U., which is a notoriously difficult switch market.”

In other recent news from Ascendis, the company announced in February that the FDA had granted Orphan Drug Designation to TransCon CNP, a long-acting prodrug of C-type natriuretic peptide (CNP) in development for children with achondroplasia. TransCon CNP is designed to address all aspects of achondroplasia by providing continuous exposure to CNP at safe, therapeutic levels in a single, weekly subcutaneous dose.

“We are pleased to receive Orphan Drug Designation for TransCon CNP in achondroplasia. Our TransCon CNP candidate is designed to address not only height, but the debilitating comorbidities of the condition,” added Leff. “In our Phase 1 trial in healthy subjects, TransCon CNP delivered continuous exposure of CNP at target levels over seven days, supporting once-weekly dosing with a well-tolerated safety profile. Based on these preliminary results, we expect to initiate a Phase 2 trial in children with achondroplasia in the third quarter of this year. In addition, as part of our commitment to the achondroplasia community, we are currently conducting the ACHieve Study, which we believe will provide important observational insights into the experience of children living with achondroplasia.”